硫氧还蛋白还原酶及其抑制剂的研究进展

Advances in thioredoxin reductase and its inhibitors

硫氧还蛋白还原酶(thioredoxin reductase,TrxR)是存在于细胞中的含硒同型二聚体黄素酶,其主要功能为调节氧化还原平衡,与细胞的增殖、凋亡以及肿瘤的发生、转移、血管生成中密切相关。含硒C末端活性位点是TrxR的特有结合域,对TrxR与底物的结合具有重要作用,其靶向抑制剂正成为治疗与肿瘤相关疾病的研究热点。本文从TrxR的结构特点及其与肿瘤相关的生理功能出发,根据其与底物结合能力进行分类,将TrxR抑制剂分为可逆和不可逆两类,对两类抑制剂的最新研究进展进行了综述。

Thioredoxin reductase （TrxR） is a seleniferous homodimeric flavoenzyme, which is ubiquitously ex- pressed in all cells and plays a crucial role in the redox regulation of numerous celluar signaling pathways in- volved in cell survival and proliferation. TrxR maintains cellular redox equilibrium. Recent researches have illumi- nated that TrxR overexpressed in many tumors, is closely associated with the evolution, progression and apoptosis of tumor. TrxR contains a reactive and solvent accessible selenocysteine residue which is located on a flexible C- terminal arm of the protein. This selenocysteine is essentially involved in the catalytic cycle of TrxR and thus re- presents an attractive binding site for inhibitors, The TrxR inhibitors as novel target-drug in cancer therapy have been extensively studied and elucidated. This article summarized the latest progress in TrxR inhibitors according to the binding capacity of TrxR and substrate.